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However, the only well\u2010documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40\u201342th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol\/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy.<\/jats:p>","DOI":"10.1002\/biof.172","type":"journal-article","created":{"date-parts":[[2011,6,15]],"date-time":"2011-06-15T10:00:55Z","timestamp":1308132055000},"page":"272-279","source":"Crossref","is-referenced-by-count":32,"title":["More folic acid, the five questions: Why, who, when, how much, and how"],"prefix":"10.1002","volume":"37","author":[{"given":"Pierpaolo","family":"Mastroiacovo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Leoncini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,14]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7135.894"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.03.064"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.573410"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.348"},{"key":"e_1_2_4_6_2","first-page":"CD006612","article-title":"Homocysteine lowering interventions for preventing cardiovascular events","volume":"4","author":"Marti\u2010Carvajal A. 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